The research objectives of this group revolve around the use of multinuclear Magnetic Resonance (NMR) techniques to elucidate the solution structure, dynamics and mechanism of action of a variety of enzymes and proteins. This approach allows one to focus on a particular aspect of a complex system, the active site of an enzyme, intermediates in the enzyme mechanism, and the structural backbone of nucleic acids. Very often this approach requires the incorporation of specifically labeled probes by chemical or biosynthetic means. A total of 56 magnetic resonance probes have been incorporated into Escherichia coli alkaline phosphatase (AP) (gamma-13C histidine, m-fluorotyrosine, p-fluorophenylalanine, and 113Cd2 plus) to study the nature and occupancy of the metal binding sites and their participation in ligand (phosphate) binding stoichiometry. Using 13C enriched iodoacetic acid, we have studied the mechanism of carboxymethylation of histidine 200 in human carbonic anhydrase B and the structure of the active site of this enzyme. Substitution of 113 Cd2 plus for the intrinsic Zn 2 plus ion(s) of a variety of metalloenzymes (alkaline phosphatase, carbonic anhydrases, carboxypeptidase and superoxide dismutase) has allowed direct observation by NMR of the metal ion and its role in the enzyme catalytic mechanism. 1H NMR has been used to study the solution structure of Gene 5 protein from bacteriophage fd and its complexes with oligodeoxynucleotides. Simplification and complete assignment of the aromatic protons in this protein has been achieved by the incorportation of specifically deuterated aromatic residues. 31P NMR studies of E. coli ribosomes, subunits and rRNA have revealed a higher degree of internal motion of the diester phosphate than has previously been supposed. 31P NMR has also been employed to study the solution structure and dynamics of nucleosomes and DNA.